Kras-LSL-G12D
系統名
C57BL/6Smoc-Krasem4(LSL-G12D)Smoc
SMOC番号
NM-KI-190003
維持形態
Repository Live
遺伝子の概要
Gene Symbol
Kras
説明
病気の予測
表現型データ
Pancreatic ductal adenocarcinoma
The KPC mouse is an established and clinically relevant model of pancreatic ductal adenocarcinoma (PDAC) which develops many key features observed in human PDAC including pancreatic intraepithelial neoplasia alongside a robust inflammatory reaction including exclusion of effector T cells. Metastases are observed in around 80% of KPC animals located primarily in the liver and lungs. Mutations in both KRAS and TP53 genes are found in around 80% and 70% of all human PDACs respectively.
Trp53-(R172H) (NM-KI-18028)、Kras-(LSL-G12D) (NM-KI-190003)were crossed with Pdx1-Cre-Tg to generate KPC mice.
Fig1. The spontaneous pancreatic tumor of KPC mouse model with large volume, uneven surface and multiple nodular projections.
Fig2. H&E staining of pancreatic tumor from KPC mouse model.
The tumor cells from KPC mouse model demonstrated disorderly arranged pancreatic cells, irregular tissue structure, dilated pancreatic ducts, inflammatory cells infiltration and stromal fibrosis as was seen in pancreas adenocarcinoma.
Fig3. Changes in pancreatic tumor volume of tumor-burdened mice.
Wild-type mice were inoculated with pancreatic tumor cells from KPC mice, and pancreatic tumors grew in size over time.
lung cancer model
Lung tumors in mice can be genetically induced by the expression of oncogenes in pulmonary cells. A popular model is KrasLSL-G12D/+ mice that express the Kras G12D oncogene in pulmonary cells after Adeno-Cre or Lenti-Cre inhalation.
This KrasLSL-G12D/+ strain of SMOC carries a point mutation (G12D) whose expression is blocked by the presence of a loxP-flanked stop codon. Homozygotes die in utero.
Cre-mediated recombination can excise the stop codon and permit the oncogenic protein to be expressed. Lung infection with an adenovirus encoding Cre results in a very high frequency of lung tumors(Fig. 1). This strain may be useful in studies of lung cancer and development.
Fig1. Mice were anesthetized and administered AAV-Cre virus by intratracheal injection.
After 3 months, CT scan analysis of the lungs revealed significant tumor formation (arrow marks) in 42# mice.
Fig2. CT scan analysis of Scgb1a1CreERT2/+; KrasG12D/+mice.
The mice were intraperitoneally injected with corn oil/tamoxifen 5 times, and their lungs were examined by CT 5 months later.
Fig3. H&E staining results of lung tissue of Scgb1a1CreERT2/+; KrasG12D/+mice.
The tumors are lung adenocarcinoma (Indicated by black arrow). Grade I and Grade IV : grading of animal tumor.
We have developed the mouse allograft lung cancer model (Fig. 4) from Kras(LSL-G12D/+) mice administered with AAV-Cre virus by intratracheal injection (Fig. 1). The mouse allograft lung cancer model grew robustly (Fig. 4) and it can provide improved operational simplicity needed for efficacy studies .
Fig4. The growth of tumors in C57BL/6 mice inoculated with lung cancer tumor from 42# mice.
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